Supporting Information

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1 Supporting Information Wiley-VCH Weinheim, Germany

2 First Catalytic Enantio- and Diastereoselective Formation of β-sultones: Ring-Strained Precursors for Enantioenriched β- Hydroxysulfonyl Derivatives Florian M. Koch and René Peters* Laboratorium für rganische Chemie, ETH Zürich, Hönggerberg HCI E 111, Wolfgang-Pauli-Str. 1, CH-893 Zürich, Switzerland peters@org.chem.ethz.ch S1

3 Table of Contents Experimental... 3 Purification of ethyl glyoxylate... 5 Activation of Lewis acid triflates... 5 General procedure for the formation of β-trichloromethyl β-sultones (GP1) Methyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2a) Ethyl-4-trichlormethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2b) Propyl-4-trichlormethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2c) (2-Chloroethyl)-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2d) Benzyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2e) (2-(4-Methoxyphenoxy)ethyl)-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2f) (2-(4-Methoxyphenyloxy)ethyl)-4-ethyloxycarbonyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2g) General procedure for the deuteration experiments (GP2) α-monodeutero ethanesulfonic acid methyl ester (1a) α-monodeutero propanesulfonic acid methyl ester (1b) ,4,4-Trichloro-3-hydroxybutane-2-sulfonic acid phenethyl ester (11a) ,1,1-Trichloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (11b) ,1,1-Trichloro-2-hydroxyhexane-3-sulfonic acid phenethyl ester (11c) ,1,1-Trichloro-2-hydroxypentane-3-sulfonic acid ethyl ester (12) ,1,1-Trichloro-3-(morpholine-4-sulfonyl)-butan-2-ol (13) and 4,4,4-Trichloro-3- morpholin-4-yl-butane-2-sulfonic acid (19) Benzenesulfonyl-1,1,1-trichlorobutan-2-ol (14a) Benzenesulfonyl-1,1,1-trichloropentan-2-ol (14b) Benzenesulfonyl-1,1,1,5-tetrachloropentan-2-ol (14d) ,1,1-trichloro-4-phenyl-3-(phenylsulfonyl)butan-2-ol (14e) Hydroxy-3-sulfopentanoic acid methyl ester (S)-( )-N,N-dimethyl-1- phenylethylammonium salt (16) ,1-Dichloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (17) Chloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (18)... 3 S2

4 Experimental Except as otherwise indicated, all reactions were carried out in oven dried glassware under a positive pressure of nitrogen. Benzene (Fluka, >99.5%) was stored in crown-capped bottles under argon over 4Å molecular sieves. Dichloromethane was purified by distillation and dried by a passage over activated alumina under nitrogen atmosphere. Methanol (Fluka, HPLC grade), pentane (J.T. Baker, UV quality), n-hexane (Fluka, UV quality), cyclohexane (Thommen & Furler), ethyl acetate (Thommen & Furler) and triethylamine (Fluka, >99.5%) were used as purchased. Ethyl glyoxylate was purchased from Fluka as 5% solution in toluene and purified as detailed below. All other laboratory chemicals were purchased from Fluka, Merck, J.T. Baker, ABCR or Aldrich and were used without purification. For work-up procedures and flashchromatography, distilled technical grade-solvents were used. Unless otherwise indicated, all liquids were added via syringe, solids were added neat against an argon flow. Solvents were removed at a heating-bath temperature of 4 C and 6-3 mbar pressure by rotary evaporation. Non-volatile compounds were dried in vacuo at.1 mbar. Yields refer to purified compounds and are calculated in mol% of the used starting material. Except as otherwise indicated, reactions were magnetically stirred and monitored by thin layer-chromatography (TLC) using silica gel plates from Merck (silica gel 6 F 254 ). Visualization occurred by fluorescence quenching under UV light and by staining with KMn 4 / NaH. Purification by flash-chromatography was performed on silica gel 6 Å, 32-62, provided by Fluka, using a forced flow of eluent at.2-.4 bar pressure. NMR-spectra were recorded on a Varian Gemini 3 and a Varian Mercury 3 spectrometer operating at 3 MHz ( 1 H), 75 MHz ( 13 C) or by the NMR service of the Laboratory of rganic Chemistry at ETHZ on a Bruker DRX4 spectrometer 4 MHz ( 1 H), 1 MHz ( 13 C). Chemical shifts δ are referred in terms of ppm and J-coupling constants are given in Hz. Abbreviations for multiplicity are as follows: s (singulet), d (doublet), t (triplet), q (quadruplet), m (multiplet), b (broad signal). IR-spectra were recorded on S3

5 a Perkin Elmer Spectrum RX I FT-IR and the signals are given by wave numbers (cm 1 ). ptical rotation was measured on a Jasco DIP-1 digital Polarimeter operating at the sodium D line with a 1 mm path length cell. Melting points were measured using a Büchi 535 melting point apparatus in open glass capillaries and are uncorrected. Mass spectra were obtained from the ETH Zürich MS Service. High resolution EI mass spectra were performed on a Micromass AutoSpec Ultima and were calibrated with perfluorotributylamine (PFTBA) prior to data acquisition. High resolution ESI mass spectra were performed on an Ion Spec Ultima 2 FTICR. ESI mass spectra were performed on a Finnigan TSQ7. Combustion analysis was performed by the Mikroelementaranalytisches Laboratorium at ETH Zürich. The single crystal X-ray analysis was performed by Paul Seiler at the ETH Zürich. S4

6 Purification of ethyl glyoxylate To a flame-dried 25 ml round bottom flask equipped with a magnetic stirring bar and a short path distillation apparatus was added 1 ml of commercial ethyl glyoxylate solution (5% in toluene) and 3 g of phosphorus pentoxide. The distillation pot was warmed to 8 9 C at 25 mbar to remove most of the toluene and to depolymerize the technical ethyl glyoxylate. The pressure was reduced to 2 mbar and the distillation pot slowly warmed to C to collect a glyoxylate/toluene mixture. The concentration of the distilled solution of monomeric glyoxylate was determined by 1 H-NMR to be typically between 55 and 75% (m/m). Activation of Lewis acid triflates All Lewis acids employed were dried using a Büchi Kugelrohr oven. The metal triflate salts were placed in a flame dried round bottomed flask and heated to 14 C at.1 mbar until weight constancy (usually overnight). The activated Lewis acids were stored and handled in a glove box. S5

7 General procedure for the formation of β-trichloromethyl β-sultones (GP1) A suspension of M(Tf) 3 (.137 mmol,.36 equiv.; M = Bi: 9 mg; M = In: 77 mg) in 1 ml DCM was sonicated at rt for 15 min and was subsequently cooled to 15 C (EtH/ice bath). Then a solution of chloral (6a, 99 μl, 1.18 mmol, 2.75 equiv.) in DCM (.5 ml) was added. After 5 min a solution of (DHQ) 2 PYR (diydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether, 3 mg,.34 mmol,.91 equiv.) in DCM (.5 ml) was added followed after additional 5 min by a solution of PMP (1,2,2,6,6-pentamethylpiperidine, 89 μl,.493 mmol, 1.32 equiv.) in DCM (.5 ml). After another 15 min of stirring at 15 C a solution of the corresponding sulfochloride 3 (.371 mmol, 1 equiv.) in DCM (.5 ml) was added dropwise by syringe pump over a period of 2.5 h. After complete addition the reaction mixture was stirred at 15 C for additional 15 min. Prior to aqueous work up the suspension was diluted with MTBE. The precipitate was filtered off and washed 4 times with MTBE. The organic layer was subsequently sequentially washed with saturated aqueous Na 2 EDTA (25 ml),.5 M H 2 S 4 (2 x 2 ml) and H 2 (2 x 1 ml). The combined organic layers were dried over MgS 4, filtered and the solvent removed in vacuo. S6

8 3-Methyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2a) Me.9 eq (DHQ)2PYR,.18 eq M(Tf) S + 3 S Cl H EtNiPr 2, DCM, 15 C Me 3a 6a 2a 3-Methyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (3a) was prepared according to GP1, but using EtNiPr 2 instead of PMP and.18 equiv. of M(Tf) 3 instead of.36 equiv.. 2a was furnished as colorless needles (M = Bi: 63 mg,.263 mmol, yield: 78%, ee = 67%, dr = 96:1; M = In: 53 mg,.21 mmol, yield: 61%, ee = 78%, dr > 1:1). The ee values were determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) after ring opening with 2-phenethyl alcohol providing phenethyl sulfonate 11a (vide infra) C C 4 H 5 Cl 3 3 S, MW: g/mol. Mp: C. [α] (c =.95, CHCl3) = ±.33 (sample with ee = 8%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = 5.21 (m, 1 H, CH-S); 5.8 (d, J = 8.2, 1 H, CH-); 1.92 (d, J = 7.4, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = 94.3 ( ); 73.5 (C ring ); 72.6 (C ring ); 9.4 (CH 3 ). IR (film): ν = 2977, 236, 1367, 1212, 1178, 945. MS (EI) m/z: 25 (.8), 23 (1), 125 (35), 123 (57), 121 (73), 119 (12), 117 (14), 92 (12), 87 (2), 65 (12), 63 (16), 57 (4), 51 (14), 41 (26), 29 (1), 27 (3). Anal. Calcd. for C 4 H 5 Cl 3 3 S: C, 2.6; H, 2.1;, 2.4; S, 13.39; Cl, Found: C, 2.35; H, 2.1;, 19.9; S, 13.21; Cl, D S7

9 3-Ethyl-4-trichlormethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2b) Et.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H PMP, DCM, 15 C Et 3b 6a 2b 3-Ethyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2b) was prepared according to GP1 In case of M = In only.18 equiv. of M(Tf) 3 instead of.36 equiv. were used. 3b was furnished as colorless needles (M = Bi: 62 mg,.245 mmol, yield: 65%, ee = 92%, dr > 1:1; M = In: 27 mg,.17 mmol, yield: 29%, ee = 97%, dr > 1:1). The ee values were determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) after ring opening with 2-phenethyl alcohol providing phenethyl sulfonate 11b (vide infra) C C 5 H 7 Cl 3 3 S, MW: g/mol. Mp: C. [α] (c = 1.125, CHCl3) = ±.39 (sample with ee = 92%). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = 5.6 (d, J = 8.3, 1 H, CH-); (m, 1 H, CH-S); (m, 1 H, CHH); (m, 1 H, CHH); 1.19 (t, J = 7.3, 3 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = 94.4 ( ); 8.2 (C ring ); 73.9 (C ring ); 18.1 (CH 2 ); 12.8 (CH 3 ). IR (CHCl 3 ): ν = 1461, 1382, 126. MS (ESI) m/z: 39 [M+MeH+Na] +. Anal. Calcd. for C 5 H 7 Cl 3 3 S: C, 23.69; H, Found: C, 23.79; H, D S8

10 3-Propyl-4-trichlormethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2c) npr.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H PMP, DCM, 15 C npr 3c 6a 2c 3-Propyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2c) was prepared according to GP1 as colorless solid (M = Bi: 47 mg,.176 mmol, yield: 47%, ee = 83%, dr > 5:1; M = In: 36 mg,.134 mmol, yield: 36%, ee = 89%, dr > 5:1). The ee values were determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) after ring opening with 2- phenethyl alcohol providing phenethyl sulfonate 11c (vide infra) C C 6 H 9 Cl 3 3 S, MW: g/mol. Mp: C. [α] (c = 1.55, CHCl3) = ±.16 (sample with ee = 83%). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 2 H, CH- S, CH-); (m, 1 H, CH 2 -CH ring ); (m, 1 H, CH 2 -CH ring ); (m, 2 H, CH 2 -CH 3 ); 2.64 (t, J = 7.4, 3 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = 94.5 ( ); 78.4 (C ring ); 73.7 (C ring ); 26.1 (CH 2 ); 21.7 (CH 2 ); 13.4 (CH 3 ). IR (CHCl 3 ): ν = 2968, 2938, 2879, 1466, MS (EI) m/z: 187 [MH-S 3 ] + (.45), 149 [MH- ] + (54), 19 (37), 85 (44), 67 (55), 55 (97). HRMS (EI) m/z: Calc. for [MH] + : Found: Anal. Calcd. for C 6 H 9 Cl 3 3 S: C, 26.93; H, Found: C, 26.94; H, D S9

11 3-(2-Chloroethyl)-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2d) Cl.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H PMP, DCM, 15 C 3d 6a 2d Cl 3-(2-Chloroethyl)-4-trichlormethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2d) was prepared according to GP1 as colorless needles (M = Bi: 93 mg,.323 mmol, yield: 87%, ee = 95%, dr > 5:1; M = In: 62 mg,.215 mmol, yield: 58%, ee = 81%, dr = 15:1). The ee values were determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) after ring opening with phenylmagnesium bromide providing phenyl sulfone 14d (vide infra) C C 5 H 6 Cl 4 3 S, MW: g/mol. Mp: C. [α] (c =.95, CHCl3) = ± H NMR (4 MHz, CDCl 3, 21 C): δ = 5.36 (ddd, J = 11.5, 8.4, 2.9, 1 H, CH-S); 5.14 (d, J = 8.4, 1 H, CH-); 3.78 (ddd, J = 11.7, 6., 4.8, 1 H, CH 2 -Cl); 3.64 (ddd, J = 11.7, 9.1, 3.9, 1 H, CH 2 -Cl); 3.17 (dddd, J = 15.5, 11.5, 6., 3.9, 1 H, CH 2 -CH ring ); 2.69 (dddd, J = 15.5, 9.1, 4.8, 3., 1 H, CH 2 -CH ring ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = 94.2 ( ); 74.9 (C ring ); 73.2 (C ring ); 41.6 (CH 2 Cl); 27.4 (CH 2 C ring ). IR (CHCl 3 ): ν = 352, 2952, 2845, 1467, 1433, 123. MS (ESI) m/z: 663 [2xM+2xMeH+Na] +, 343 [M+MeH+Na] +. Anal. Calcd. for C 5 H 6 Cl 4 3 S: C, 2.85; H, 2.1. Found: C, 21.8; H, D S1

12 3-Benzyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide (2e) Ph.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H PMP, DCM, 15 C 3e 6a Ph 2e 3-Benzyl-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide 2e was prepared according to GP1 as colorless solid (M = Bi: 7 mg,.223 mmol, yield: 6%, ee = 91%, dr = 22:1; M = In: 67 mg,.211 mmol, yield: 57%, ee = 84%, dr > 12:1). The ee values were determined by HPLC (Chiralcel D-H, 98:2 n-hexane/iprh, 1. ml/min) C C 1 H 9 Cl 3 3 S, MW: g/mol. Mp: C. [α] (c =.35, CHCl3) = ± 1.2 (sample with ee > 99.5% after recrystalization). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 5 H, CH Ph ); 5.27 (ddd, J = 12.3, 8.3, 3.1, 1 H, CH-S); 5.13 (d, J = 8.3, 1 H, CH-); 3.96 (dd, J=15., 12.3, 1 H, CH 2 ); 3.52 (dd, J = 15., 3.1, 1 H, CH 2 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); (C Ph ); (C Ph ); 128. (C Ph ); 94.4 ( ); 79.7 (C ring ); 73.9 (C ring ); 3.5 (CH 2 ). IR (CHCl 3 ): ν = 163, 1498, 1456, MS (EI) m/z: 314 [M] +, 197 [M- ] + (18), 133, 91 [C 7 H 7 ] +, 77 [C 6 H 5 ] +. HRMS (EI) m/z: Calc. for [M] + : Found: Anal. Calcd. for C 1 H 9 Cl 3 3 S: C, 38.6; H, Found: C, 38.15; H, D S11

13 3-(2-(4-Methoxyphenoxy)ethyl)-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2- dioxide (2f) Me.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H PMP, DCM, 15 C 3f 6a 2f Me 3-(2-(4-Methoxyphenoxy)ethyl)-4-trichloromethyl-1-oxa-2-thiacyclobutan-2,2-dioxide 2f was prepared according to GP1 as colorless needles (M = Bi: 116 mg,.38 mmol, yield: 83%, ee = 99.4%, dr > 1:1; M = In: 96 mg,.256 mmol, yield: 69%, ee = 99.2%, dr > 1:1). The ee values were determined by HPLC (Chiralcel D-H, 96:4 n-hexane/eth, 1. ml/min) C C 12 H 13 Cl 3 5 S, MW: g/mol. Mp: C. [α] (c =.923, CHCl3) = ± H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 4 H, CH Ph ); (m, 1 H, CH-S); 5.11 (d, J = 8.4, 1 H, CH-); (m, 1 H, CH 2 -Ar); 4.2 (ddd, J = 9.3, 7.9, 4.2, 1 H, CH 2 -Ar); 4.2 (s, 3 H, CH 3 ); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 -C ring ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); (C Ph ); (2x CH Ph ); (2x D CH Ph ); 94.6 ( ); 75.8 (C ring ); 73.4 (C ring ); 65.4 (CH 2 ); 55.7 (CH 3 ); 24.8 (CH 2 C ring ). IR (CHCl 3 ): ν = 162, 159, MS (EI) m/z: 374 [M] +, 294 [M-S 3 ] +, 137, 123. HRMS (EI) m/z: Calc. for [M] + : Found: Anal. Calcd. for C 12 H 13 Cl 3 5 S: C, 38.87; H, Found: C, 38.87; H, S12

14 3-(2-(4-Methoxyphenyloxy)ethyl)-4-ethyloxycarbonyl-1-oxa-2-thiacyclobutan-2,2- dioxide (2g) Me.9 eq (DHQ)2PYR,.36 eq M(Tf) S + 3 S Cl H C 2 Et PMP, DCM, 15 C C 2 Et 3f 6b 2g Me A suspension of M(Tf) 3 (.144 mmol,.36 equiv., M = Bi: 9 mg; M = In: 77 mg) in DCM (1 ml) was sonicated at room temperature for 15 min and was subsequently cooled to 15 C (EtH/ice bath). Then a solution of (DHQ) 2 PYR (3 mg,.34 mmol,.91 equiv.) in DCM (.5 ml) was added followed after additional 5 min by a solution of PMP (89 μl,.493 mmol, 1.32 equiv.) in DCM (.5 ml). After another 15 min of stirring at 15 C a solution of sulfochloride 3f (11 mg,.383 mmol, 1 equiv.) in DCM (.5 ml) and ethyl glyoxylate (6b, 1.29 mmol, 2.69 equiv.) as solution in a mixture of toluene (see purification of ethyl glyoxylate) and DCM (solvent amount in total.5 ml) were simultaneously added dropwise by syringe pump over a period of 2.5 h. Finally the reaction mixture was stirred at 15 C for additional 15 min. Prior to aqueous work up the suspension was diluted with MTBE. The precipitate was filtered off and washed 4 times with MTBE. The organic layer was afterwards sequentially washed with saturated aqueous Na 2 EDTA (25 ml),.5 M H 2 S 4 (2 x 2 ml) and H 2 (2 x 1 ml). The combined organic layers were dried over MgS 4, filtered and the solvent removed in vacuo. Flash column chromatography on silica (eluent DCM) furnished analytically pure sultone 2g as a hygroscopic colorless solid (M = Bi: 65 mg,.193 mmol, yield: 52%, ee = 9%, dr = 2:1; M = In: 78 mg,.236 mmol, yield: 62%, ee = 9%, dr = 2.5:1). The ee values were determined by HPLC (Chiralcel D-H, 96:4 n-hexane/eth, 1. ml/min). 2g was found to be both acid and base labile. Even traces of acid in the isolated product initiate an autocatalytic decomposition / S13

15 oligomerization whereas bases like triethylamine lead to elimination products. Therefore excessive drying was not possible and analytics were carried out immediately after purification C C 14 H 18 7 S, MW: g/mol. Mp: C. [α] (c =.15, CH2Cl 2 ) = ±.71 (sample with ee = 9%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = 6.83 (s, 4 H, CH Ph ); 5.36 (m, 1 H, CH-S); 4.99 (d, J = 8.7, 1 H, CH-); 4.38 (qd, J = 7.2, 1.9, 2 H, CH 2 - ester ); (m, 2 H, CH 2 -Ar); 3.77 (s, 3 H, CH 3 ); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 - C ring ); 1.38 (t, J = 7.2, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C=); (C Ph ); (C Ph ); (2x CH Ph ); (2x CH Ph ); 75.3 (C ring ); 64.5 (CH 2 ); 63.2 (C ring ); 63. (CH 2 ); 55.7 (CH 3 ); 26.2 (CH 2 C ring ); 14.2 (CH 3 CH 2 ). IR (CHCl 3 ): ν = 2937, 1766, 1739, 159, 1378, 142. MS (EI) m/z: 33 [M] + (62), 27 [M-PhMe] + (43), 179 (46), 127 (1), 124 [HPhMe] + (63), 123 [PhMe] + (51), 99 (86). HRMS (EI) m/z: Calc. for [M] + : Found: D S14

16 General procedure for the deuteration experiments (GP2) A suspension of Bi(Tf) 3 (5 mg,.76 mmol,.18 equiv.) in DCM (.5 ml) was sonicated at room temperature for 15 min and was subsequently cooled to 15 C (EtH/ice bath). Then a solution of d1-med (31 μl,.756 mmol, 1.85 equiv.) in DCM (.5 ml) was added. After 5 min a solution of (DHQ) 2 PYR (33 mg,.38 mmol,.9 equiv.) in DCM (.5 ml) was added followed after additional 5 min by a solution of PMP (99 μl,.416 mmol, 1.33 equiv.) in DCM (.5 ml). After another 15 min of stirring at 15 C a solution of the corresponding sulfochloride 3 (.416 mmol, 1 equiv.) in DCM (.5 ml) was added dropwise by syringe pump over a period of 2.5 h. After complete addition the reaction mixture was stirred at 15 C for additional 15 min. Prior to aqueous work up the suspension was diluted with MTBE. The precipitate was filtered off and washed 4 times with MTBE. The organic layer was subsequently sequentially washed with saturated aqueous Na 2 EDTA (25 ml),.5 M H 2 S 4 (2 x 2 ml) and H 2 (2 x 1 ml). The combined organic layers were dried over MgS 4, filtered and the solvent removed in vacuo. α-monodeutero ethanesulfonic acid methyl ester (1a) Me S Cl + MeD.1 (DHQ) 2 PYR,.2 Bi(Tf) 3, PMP, DCM, 15 C Me S Me D 3a 1a α-monodeutero ethanesulfonic acid methyl ester 1a was obtained according to GP2 from ethanesulfonyl chloride (3a, 39 μl) as a pink volatile liquid (crude: 6 mg,.87 mmol of 1a as determined by 1 H-NMR, yield: 21%, deuteration level 57% (determined by GC-MS)) containing 13% of unreacted sulfochloride 3a and 69% of MTBE. Excessive drying was avoided S15

17 to prevent further loss of the volatile methyl ester 1a. The analytical data were in accordance with literature precedent. 1 α-monodeutero propanesulfonic acid methyl ester (1b) Et S Cl + MeD.1 (DHQ) 2 PYR,.2 Bi(Tf) 3, PMP, DCM, 15 C Et S Me D 3b 1b α-monodeutero ethanesulfonic acid methyl ester 1b was obtained according to GP2 from propanesulfonyl chloride (3b, 47 μl) as a pink volatile liquid (crude: 5 mg,.146 mmol, yield: 35% of 1b as determined by 1H-NMR, deuteration level 88% (determined by GC-MS)) containing 46% of unreacted sulfochloride 3a and 13% of MTBE. Excessive drying was avoided to prevent further loss of the volatile methyl ester 1b. The analytical data were in accordance with literature precedent. 1 1 a) J. F. King, T. Durst, J. Am. Chem. Soc. 1965, 87, 5684; b) W. E. Truce, R. W. Campbell, J. Am. Chem. Soc. 1966, 88, S16

18 4,4,4-Trichloro-3-hydroxybutane-2-sulfonic acid phenethyl ester (11a) S Me 2a BnCH 2 H, NEt 3, Et 2 Ph S 11a Me H To a stirred solution of β-sultone 2a (23 mg,.86 mmol, 1 equiv.) in Et 2 (.25 ml) a solution of 2-phenethyl alcohol (26 μl,.216 mmol, 2.5 equiv.) in Et 2 (.15 ml) was added at room temperature followed by NEt 3 (12 μl,.86 mmol, 1 equiv.) in Et 2 (.15 ml). After stirring the reaction mixture at room temperature for 14 h, the solvent was removed in vacuo. Flash column chromatography on silica (cyclohexane / EtAc 4 : 1) furnished pure phenethyl ester 11a as colorless oil (26 mg,.72 mmol, 84%, ee = 78%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) C C 12 H 15 Cl 3 4 S, MW: g/mol. [α] (c = 1.3, CHCl3) = ±.6 (sample with ee D = 78%). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 5 H, CH Ph ); (m, 1 H, CH-H); 4.5 (dt, J = 6.9,.7, 2 H, CH 2 -); 3.85 (dq, J = 7., 1.1, 1 H, CH-S); (m, 1 H, -H); 3.8 (t, J = 6.9, 2 H, CH 2 -Ph); 1.57 (d, J = 7., 3 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); 129. (2x CH Ph ); (2x CH Ph ); (CH Ph ); 11.3 ( ); 78.5 (C ring ); 7.6 (CH 2 ); 57.8 (C ring ); 35.7 (CH 2 Ph); 9. (CH 3 ). IR (CHCl 3 ): ν = 3588, 337, 1456, 1355, 1336, HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 12 H 15 Cl 3 4 S: C, 39.85; H, Found: C, 39.73; H, S17

19 1,1,1-Trichloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (11b) S Et 2b BnCH 2 H, NEt 3, Et 2 Ph S 11b Et H To a stirred solution of β-sultone 2b (25 mg,.94 mmol, 1 equiv.) in Et 2 (2 ml) a solution of 2-phenethyl alcohol (28 μl,.234 mmol, 2.5 equiv.) in Et 2 (.25 ml) was added at room temperature followed by NEt 3 (13 μl,.94 mmol, 1 equiv.) in Et 2 (.25 ml). The flask was subsequently closed. After stirring the reaction mixture at 5 C for 3 h, the solvent was removed in vacuo. Excess of phenethyl alcohol was removed by flash column chromatography on silica (cyclohexane / EtAc 4 : 1). Unconverted sultone was removed afterwards by flash column chromatography on silica (DCM), furnishing the pure phenethylester 11b as colorless oil (22 mg,.59 mmol, 62%, ee = 9%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) C C 13 H 17 Cl 3 4 S, MW: g/mol. [α] (c =.75, CHCl3) = ±.21 (sample with ee D = 9%). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 4 H, CH Ph ); (m, 1 H, CH-H); 4.51 (t, 2 H, CH 2 -); 3.57 (ddd, J = 8.5, 2.3, 2.2, 1 H, CH-S); (m, 3 H, CH 2 - Ph, -H); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 -C ring ); 1.19 (t, J = 7.5, 3 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); 129. (2x CH Ph ); (2x CH Ph ); (CH Ph ); 11.3 ( ); 79.2 (C ring ); 7.1 (CH 2 ); 64.2 (C ring ); 35.7 (CH 2 Ph); 17.7 (CH 2 - C ring ); 13.3 (CH 3 ). IR (CHCl 3 ): ν = 3587, 164, 1498, 1456, 1334, 1164 cm -1. MS (ESI) m/z: 773 [2xM+Na] +, 399 [M+Na] +. Anal. Calcd. for C 13 H 17 Cl 3 4 S: C, 41.56; H, Found: C, 41.6; H, 4.6. S18

20 1,1,1-Trichloro-2-hydroxyhexane-3-sulfonic acid phenethyl ester (11c) S npr 2c BnCH 2 H, NEt 3, Et 2 Ph S 11c npr H To a stirred solution of β-sultone 2c (28 mg,.94 mmol, 1 equiv.) in Et 2 (1 ml) a solution of 2-phenethyl alcohol (56 μl,.471 mmol, 5 equiv.) in Et 2 (.25 ml) was added at room temperature followed by NEt 3 (13 μl,.94 mmol, 1 equiv.) in Et 2 (.25 ml). The flask was subsequently closed. After stirring the reaction mixture at 5 C for 18 h, the solvent was removed in vacuo. Excess of phenethyl alcohol was removed by flash column chromatography on silica (cyclohexane / EtAc 4 : 1). Unconverted sultone was removed afterwards by flash column chromatography on silica (DCM), furnishing the pure phenethylester as colorless oil (28 mg,.72 mmol, 76%, ee = 89%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) C C 14 H 19 Cl 3 4 S, MW: g/mol. [α] (c =.55, CHCl3) = ±.13 (sample with ee D = 89%). 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 5 H, CH Ph ); 4.66 (dd, J = 5.3, 1., 1 H, CH-H); 4.44 (t, J = 6.9, 2 H, CH 2 -); 3.61 (ddd, J = 8.6, 2.2, 1., 1 H, CH-S); 3.7 (d, J = 5.3, 1 H, -H); 3.3 (t, J = 6.9, 2 H, CH 2 -Ph); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 CH 3 ); (m, 1 H, CH 2 CH 3 );.86 (t, J = 7.3, 3 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); 129. (2x CH Ph ); (2x CH Ph ); (CH Ph ); 11.3 ( ); 79.2 (C ring ); 7.1 (CH 2 ); 62.4 (C ring ); 35.7 (CH 2 Ph); 26. (CH 2 -C ring ); 21.8 (CH 2 CH 3 ); 14. (CH 3 ). IR (CHCl 3 ): ν = 3586, 2966, 2877, 1456, 1337, 117. MS (ESI) m/z: 413 [M+Na] +. Anal. Calcd. for C 14 H 19 Cl 3 4 S: C, 43.15; H, Found: C, 43.22; H, 5.1. S19

21 1,1,1-Trichloro-2-hydroxypentane-3-sulfonic acid ethyl ester (12) S Et EtH, NEt 3 Et S Et 2b 12 H To a stirred solution of β-sultone 2b (27 mg, recrystallized from hexane, ee = 95% (determined as phenethyl sulfonate 11b),.16 mmol, 1 equiv.) in Et 2 (.5 ml) EtH (.5 ml) was added at room temperature followed by NEt 3 (148 μl, 1.65 mmol, 1 equiv.). After stirring the reaction mixture at room temperature for 17 h, the solvent was removed in vacuo. Flash column chromatography on silica (DCM) furnished pure ethyl ester 12 as colorless oil (17 mg,.57 mmol, 54%, ee = 96%). The ee value was determined by HPLC (Chiralcel D-H, 98:2 n- hexane/eth, 1. ml/min) C C 7 H 13 Cl 3 4 S, MW: g/mol. [α] (c =.8, CHCl3) = ±.9 (sample with ee = D 96%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = 4.85 (m, 1 H, CH-H); 4.41 (dq, J = 7.2, 2.8, 1 H, CHH-); 4.36 (dq, J = 6.85, 2.8, 1 H, CHH-); 3.61 (ddd, J = 8.4, 2.2, 1., 1 H, CH-S); 3.42 (m, 1 H, -H); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 -C ring ); 1.44 (dd, J = 7.2, 6.9, 3 H, CH 3 ); 1.22 (t, J = 7.5, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = 11.4 ( ); 79.1 (C ring ); 67.1 (CH 2 CH 3 ); 63.9 (C ring ); 17.7 (CH 2 C ring ); 15.2 (CH 3 ); 13.3 (CH 3 ). IR (CHCl 3 ): ν = 359, 35, 2987, 1466, HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 7 H 13 Cl 3 4 S: C, 28.6; H, Found: C, 28.42; H, S2

22 1,1,1-Trichloro-3-(morpholine-4-sulfonyl)-butan-2-ol (13) and 4,4,4-Trichloro-3- morpholin-4-yl-butane-2-sulfonic acid (19) morpholine, H S MeCN N S Me Me 2a 13 + N S H Me 19 To a stirred solution of β-sultone 2a (17 mg, batch with ee = 8% (determined as phenethyl sulfonate 11a),.71 mmol, 1 equiv.) in DCM (.75 ml) a solution of morpholine (62 μl,.714 mmol, 1 equiv.) in DCM (.25 ml) was added room temperature. The reaction mixture was stirred for 3 h at room temperature before removing the solvent in vacuo. Then the crude product mixture (regioselectivity 2:1) was dissolved in MeH (5 μl) and Et 2 was added until precipitation of the minor regioisomer, the hygroscopic taurine derivative 19, occurred. After standing overnight at 4 C the supernatant liquid was removed, diluted with 15 ml of Et 2 and extracted twice with 1M HCl. The combined organic layers were washed with H 2 until neutral, dried over Na 2 S 4 and filtered. After removal of the solvent in vacuo, sulfonamide 13 was obtained as colorless solid (15 mg,.45 mmol, 65%). Taurine derivative 19 was furnished without further purification as slightly brown solid (8 mg,.25 mmol, 35%) C Sulfonamide 13: C 8 H 14 Cl 3 N 4 S, MW: g/mol. [α] (c =.75, CHCl3) = ±.55 (sample with ee = 8%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 1 H, CH- H); 3.84 (dq, J = 7.2,.9, 1 H, CH-S); (m, 4 H, 2x CH 2 -); (m, 4 H, 2x CH 2 -N); 3.37 (b, 1H, -H); 1.6 (d, J = 7.2, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = 11.7 ( ); 79. (C ring ); 66.9 (CH 2 ); 58.7 (C ring ); 46.5 (CH 2 N); 9.1 (CH 3 ). IR (CHCl 3 ): ν = 3581, 2925, 2865, 1454, 134, 1225, HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 8 H 14 Cl 3 N 4 S: C, 29.42; H, Found: C, 29.5; H, Taurine derivative 19: C 8 H 14 Cl 3 N 4 S, MW: g/mol. 1 H NMR (4 MHz, CD 3 D, 21 C): δ = 4.84 (d, J = 1.2, 1 H, CH-N); (m, 4 H, 2x CH 2 -); 3.5 (dq, J = 7.2, 1.2, 1 D S21

23 H, CH-S); (m, 4 H, 2x CH 2 -N); 1.51 (d, J = 7., 3 H, CH 3 ). 13 C NMR (1 MHz, CD 3 D, 21 C): δ = 15.2 ( ); 81.1 (C ring ); 64.9 (CH 2 ); 57.7 (C ring ); 44.7 (CH 2 N); 1.7 (CH 3 ). IR (CHCl 3 ): ν = 187, 1666, 163. Anal. Calcd. for C 12 H 15 Cl 3 4 S: a satisfactory microanalysis could not be obtained due to hygroscopicity. S22

24 3-Benzenesulfonyl-1,1,1-trichlorobutan-2-ol (14a) S Me 2a PhMgBr, Et 2 Ph S Me 14a H A stirred solution of β-sultone 2a (2 mg, batch with ee = 84% (determined as phenethyl sulfonate 11a),.89 mmol, 1 equiv.) in Et 2 (1.5 ml) was cooled to 4 C. Then a solution of phenyl magnesium bromide (44 μl,.133 mmol, 3M in Et 2, 1.5 equiv.) in Et 2 (.5 ml) was added. The solution was allowed to warm up to room temperature and the flask was subsequently closed. After stirring the reaction mixture at 5 C for 15 h, it was allowed to cool down to room temperature. Then ice and HCl (1M, 3 ml) were successively added. The aqueous layer was extracted three times with Et 2, the combined organic layers were dried over Na 2 S 4, filtered and the solvent was removed in vacuo. Flash column chromatography on silica (DCM) furnished pure phenyl sulfone 14a as colorless oil (26 mg,.72 mmol, 84%, ee = 84%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.5:1.5 n-hexane/iprh, 1.5 ml/min) C C 1 H 11 Cl 3 3 S, MW: g/mol. [α] (c =.3, CHCl3) = ±.5 (sample with ee = D 84%) 1 H NMR (4 MHz, CDCl 3, 21 C): δ = (m, 2 H, CH Ph ); (m, 1 H, CH Ph ); (m, 2 H, CH Ph ); 4.97 (b, 1 H, CH-H); 3.84 (dq, J = 7., 1.1, 1 H, CH-S); 3.43 (b, 1 H, -H); 1.51 (d, J = 7., 1 H, CH 3 ). 13 C NMR (1 MHz, CDCl 3, 21 C): δ = (C Ph ); (CH Ph ); (2xCH Ph ); (2xCH Ph ); 11.7 ( ); 77.7 (C ring ); 61.2 (C ring ); 8.6 (CH 3 ). IR (CHCl 3 ): ν = 3586, 3467, 1448, 138,1151. HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 1 H 11 Cl 3 3 S: C, 37.82; H, Found: C, 38.29; H, S23

25 3-Benzenesulfonyl-1,1,1-trichloropentan-2-ol (14b) S Et 2b PhMgBr, Et 2 Ph S Et 14b H A stirred solution of β-sultone 2b (19 mg recrystallized from hexane, ee = 99.4% (determined as phenethyl sulfonate 11b),.75 mmol, 1 equiv.) in Et 2 (2 ml) was cooled to 4 C. Then a solution of phenyl magnesium bromide (37 μl,.112 mmol, 3M in Et 2, 1.5 equiv.) in Et 2 (.25 ml) was added. The solution was allowed to warm up to room temperature and the flask was subsequently closed. After stirring the reaction mixture at 5 C for 2 h, it was allowed to cool down to room temperature. Then ice and HCl (1M, 3 ml) were successively added. The aqueous layer was extracted three times with Et 2, the combined organic layers were dried over Na 2 S 4, filtered and the solvent was removed in vacuo. Flash column chromatography on silica (DCM) furnished pure phenyl sulfone 14b as colorless oil (23 mg,.69 mmol, 92%, ee = 99.5%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.8:1.2 n- hexane/iprh, 1.5 ml/min) C C 11 H 13 Cl 3 3 S, MW: g/mol. [α] (c =.32, CHCl3) = ±.79 (sample with ee D = 99.5%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 2 H, CH Ph ); (m, 3 H, CH Ph ); (m, 1 H, CH-H); 3.56 (dd, J = 7.8, 1.9, 1 H, CH-S); 3.28 (d, J = 4.7, 1 H, - H); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 -C ring );.99 (t, J = 7.5, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C Ph ); (CH Ph ); (2x CH Ph ); 129. (2x CH Ph ); 11.4 ( ); 78.4 (C ring ); 67.6 (C ring ); 16.9 (CH 2 C ring ); 13.8 (CH 3 ). IR (CHCl 3 ): ν = 3586, 2974, 2931, 1711, 138, 115. MS (EI) m/z: 33 [M] +, 189 [M-PhS 2 ] +. HRMS (EI) m/z: Calc. for [M] + : Found: Anal. Calcd. for C 11 H 13 Cl 3 3 S: C, 39.84; H, Found: C, 4.11; H, 4.1. S24

26 3-Benzenesulfonyl-1,1,1,5-tetrachloropentan-2-ol (14d) S PhMgBr, Et 2 Ph S H Cl 2d Cl 14d A stirred solution of β-sultone 2d (15 mg recrystallized from hexane,.5 mmol, 1 equiv.) in Et 2 (.5 ml) was cooled to 4 C. Then a solution of phenyl magnesium bromide (5 μl,.15 mmol, 3M in Et 2, 3 equiv.) in Et 2 (.25 ml) was added. The solution was allowed to warm up to room temperature and the flask was subsequently closed. After stirring the reaction mixture at 5 C for 15 h, it was allowed to cool down to room temperature. Then ice and HCl (1M, 3 ml) were successively added. The aqueous layer was extracted three times with Et 2, the combined organic layers were dried over Na 2 S 4, filtered and the solvent was removed in vacuo. Flash column chromatography on silica (DCM) furnished pure phenyl sulfone 14d as colorless oil (15 mg,.41 mmol, 82%, ee > 99.5%). The ee value was determined by HPLC (Chiralcel D-H, 99:1 98.4:1.6 n-hexane/iprh, 1.5 ml/min) C C 11 H 12 Cl 4 3 S, MW: g/mol. [α] (c =.6, CHCl3) = ±.15 (sample with ee > D 99.5%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 2 H, CH Ph ); (m, 3 H, CH Ph ); (m, 1 H, CH-H); 4.1 (dd, J = 8.7, 2.2, 1 H, CH-S); (m, 2 H, CH 2 Cl); 3.42 (d, J = 4.4, 1 H, -H); (m, 1 H, CH 2 -C ring ); (m, 1 H, CH 2 - C ring ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C Ph ); (CH Ph ); (2xCH Ph ); (2x CH Ph ); 1.9 ( ); 78.4 (C ring ); 62.4 (C ring ); 42.7 (CH 2 Cl); 26.7 (CH 2 -C ring ). IR (CHCl 3 ): ν = 3585, 1448, 139, 114. HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 11 H 12 Cl 4 3 S: C, 36.9; H, 3.3. Found: C, 36.39; H, S25

27 1,1,1-trichloro-4-phenyl-3-(phenylsulfonyl)butan-2-ol (14e) S Ph 2e PhMgBr, Et 2 Ph S Ph H 14e A stirred solution of β-sultone 2e (11 mg recrystallized from hexane, ee = 96%,.33 mmol, 1 equiv.) in Et 2 (1.5 ml) was cooled to 4 C. Then a solution of phenyl magnesium bromide (33 μl,.99 mmol, 3M in Et 2, 3 equiv.) in Et 2 (.3 ml) was added. The solution was allowed to warm up to room temperature and the flask was subsequently closed. After stirring the reaction mixture at 5 C for 17 h, it was allowed to cool down to room temperature. Then ice and HCl (1M, 1 ml) were successively added. The aqueous layer was extracted three times with Et 2, the combined organic layers were dried over Na 2 S 4, filtered and the solvent was removed in vacuo. Flash column chromatography on silica (DCM) furnished pure phenyl sulfone 14e as colorless oil (12 mg,.3 mmol, 9%, ee = 98%). The ee value was determined by HPLC (Chiralcel D- H, 98:2 n-hexane/iprh, 1. ml/min) C C 16 H 15 Cl 3 3 S, MW: g/mol. [α] (c =.65, CHCl3) = ± 1.12 (sample with D ee=98%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 2 H, CH Ph ); (m, 1 H, CH Ph ); (m, 2 H, CH Ph ); (m, 5 H, CH Ph ); (m, 1 H, CH-H); (m, 1 H, CH-S); 3.78 (dd, J = 16.8, 2.2, 1 H, CH 2 -C ring ); 3.58 (d, J = 4.9, 1 H, -H); 3.17 (dd, J = 16.8, 9.3, 1 H, CH 2 -C ring ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C Ph ); (C Ph ); (CH Ph ); 129. (2x CH Ph ); (4x CH Ph ); (2x CH Ph ); (CH Ph ); 11.7 ( ); 77.8 (C ring ); 66.8 (C ring ); 29.7 (CH 2 -C ring ). IR (CHCl 3 ): ν = 369, 3586, 164, 1498, 1448, 138, 1148 cm -1. HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 16 H 15 Cl 3 3 S: C, 48.81; H, Found: C, 49.2; H, S26

28 2-Hydroxy-3-sulfopentanoic acid methyl ester (S)-( )-N,N-dimethyl-1- phenylethylammonium salt (16) S Et NaH, then H + H 3 S Et H C 2 H 1. MeH 2. (S)-Me 2 NCH(Me)Ph Me Ph Me HN Me 3 S Et H C 2 Me 2b β-sultone 2b (19 mg, batch with ee = 95% (determined as phenethyl sulfonate 11b),.75 mmol, 1 equiv.) was stirred in aqueous NaH (466 μl,.466 mmol, 6.25 equiv.) at room temperature for 18h. The reaction mixture was filtered over an acidic cation exchanger resin (Amberlite IR- 12, 2.5 g) and eluted with water until neutral. Concentrating the filtrate in vacuo furnished diacid 15 as slightly yellow oil (16 mg,.75 mmol, 1 equiv.), which was dissolved in 1 ml of MeH and stirred for 14 h at room temperature. Afterwards the solvent was removed in vacuo and the residue was dried using azeotropic evaporation with toluene and subsequently with MeH (twice) to furnish the corresponding monomethylester as pale yellow oil, which was employed in the next step without purification. The ester was dissolved in MeH (1 ml) and a solution of (S)-( )-N,N-dimethyl-1-phenylethylamine (13 μl,.75 mmol, 1 equiv.) in MeH (1 ml) was added at room temperature. After 5 h the solvent was removed in vacuo. The residue was dissolved in a minimum amount of DCM and hexane was added until precipitation of the corresponding ammonium salt 16, which was obtained as a pale yellow oil (24 mg,.66 mmol, 88% over 3 steps) C C 16 H 27 N 6 S, MW: g/mol. [α] (c =1.15, CHCl3) = 5.36 ± H NMR (3 D MHz, CDCl 3, 21 C): δ = 7.45 (b, 5 H, CH Ph ); 4.86 (b, 1 H, NH + ); 4.44, 4.33 (b, 2 H, CH-H, NCHCH 3 ); 3.76 (b, 3 H, CCH 3 ); 3.49 (b, 1 H, CH-S); 3.32 (b, 1 H, -H); 2.83 (b, 3 H, NCH 3 ); 2.67 (b, 3 H, NCH 3 ); 2.19 (b, 1 H, CH 2 CH 3 ); 1.99 (b, 1 H, CH 2 CH 3 ); 1.78 (b, 3 H, CHCH 3 ); 1.11 (b, 3 H, CH 2 CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (CMe); (C Ph ); 13.4 (CH Ph ); (2xCH Ph ); (2x CH Ph ); 69.2 (CH-); 66.3 (NCHCH 3 ); S27

29 63.3 (CH-S); 52.2 (CCH 3 ); 42.3 (NCH 3 ); 39.1 (NCH 3 ); 2.3 (CHCH 3 ); 16.8 (CH 2 CH 3 ); 11.7 (CH 3 ). IR (CHCl 3 ): ν = 3423, 1745, 1459, 1243, 1144, 99. HRMS (ESI) m/z: Calc. for [Cation] + : Found: Calc. for [Anion] + : Found: Anal. Calcd. for C 16 H 27 N 6 S: a satisfactory microanalysis could not be obtained due to hygroscopicity. S28

30 1,1-Dichloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (17) Ph H Bu 3 SnH, H S THF, 65 C Ph S Cl Et Et Cl 11b 17 To a solution of sulfonate 11b (18 mg, batch with ee = 9%,.46 mmol, 1 equiv.) in THF (1.5 ml) a solution of tributyltin hydride (55 μl,.25 mmol, 4.5 equiv.) in THF (.5 ml) was added at room temperature and the flask was closed. After stirring the reaction mixture at 6 C for 14 h, the solvent was removed in vacuo. The residue was dissolved in MeCN and extracted three times with hexane to remove all tin derivatives. Flash column chromatography on silica (DCM) furnished pure dichloro sulfonate 17 as colorless oil (11 mg,.34 mmol, 7%) C C 13 H 18 Cl 2 4 S, MW: g/mol. [α] (c =.7, CHCl3) = ±.52 (sample with ee = D 9%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 5 H, CH Ph ); 5.8 (d, J = 5.9, 1 H, CHCl 2 ); (m, 2 H, CH 2 -); (m, 1 H, CH-H); (m, 1 H, CH-S); 3.8 (t, J = 6.9, 3 H, CH 2 -Ph); 2.83 (d, J = 4.4, 1 H, -H); (m, 2 H, CH 2 -C ring ); (m, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C Ph ); (2x CH Ph ); (2x CH Ph ); (CH Ph ); 74.4, 73.8 (CHCl 2, C ring ); 7.3 (CH 2 ); 63.5 (C ring ); 35.7 (CH 2 Ph); 18. (CH 2 -C ring ); 12.3 (CH 3 ). IR (CHCl 3 ): ν = 3584, 2967, 144, 1456, HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 13 H 18 Cl 2 4 S: C, 45.76; H, Found: C, 45.91; H, S29

31 1-Chloro-2-hydroxypentane-3-sulfonic acid phenethyl ester (18) Ph H Bu 3 SnH, H S toluene, 11 C Ph S Et Et 11b 18 Cl To a solution of sulfonate 11b (23 mg, batch with ee = 8%,.58 mmol, 1 equiv.) in toulene (2 ml) a solution of tributyltin hydride (55 μl,.25 mmol, 4.5 equiv.) in toluene (.5 ml) was added at room temperature and the flask was closed. After stirring the reaction mixture at 11 C for 14 h, the solvent was removed in vacuo. The residue was dissolved in MeCN and extracted three times with hexane to remove all tin derivatives. Flash column chromatography on silica (DCM) furnished pure monochloro sulfonate 18 as colorless oil (15 mg,.49 mmol, 83%) C C 13 H 19 Cl 4 S, MW: g/mol. [α] (c =.8, CHCl3) = +7.5 ±.42 (sample with ee = D 8%). 1 H NMR (3 MHz, CDCl 3, 21 C): δ = (m, 5 H, CH Ph ); (m, 2 H, CH 2 -); (m, 1 H, CH-H); 3.63 (dd, J = 11.2, 6.5, 1 H, CH 2 Cl); 3.5 (dd, J = 11.2, 6.5, 1 H, CH 2 Cl); (m, 1 H, CH-S); 3.8 (t, J = 6.9, 3 H, CH 2 -Ph); 2.75 (d, J = 4.7, 1 H, -H); (m, 2 H, CH 2 -C ring ); (m, 3 H, CH 3 ). 13 C NMR (75 MHz, CDCl 3, 21 C): δ = (C Ph ); (2x CH Ph ); (2x CH Ph ); (CH Ph ); 7.2 (CH 2 ); 69.7 (C ring ); 64.1 (C ring ); 45.2 (CH 2 Cl); 35.6 (CH 2 Ph); 17.5 (CH 2 -C ring ); 12.6 (CH 3 ). IR (CHCl 3 ): ν = 3568, 2964, 1456, 135, HRMS (ESI) m/z: Calc. for [M+Na] + : Found: Anal. Calcd. for C 13 H 19 Cl 4 S: C, 5.89; H, Found: C, 5.74; H, S3

32 S Me 2a

33 S Et 2b

34 S npr 2c

35 S 2d Cl

36 S Ph 2e

37 S 2f Me

38 S C 2 Et 2g Me

39 H Ph S Me 11a

40 H Ph S Et 11b

41 H Ph S npr 11c

42 H Et S Et 12

43 H N S Me 13

44 H Ph S Me 14a

45 H Ph S Et 14b

46 H Ph S Cl 14d

47 H Ph S Ph 14e

48 Me Me H Ph HN Me 3 S C 2 Me Et 16

49 H Ph S Cl 17 Et Cl

50 H Ph S Cl 18 Et

51 N H S Me 19

52 Area % Report Page 1 of 1 Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK46-125rohkochSulfonatII.met PM.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 3/23/26 12:24:54 PM Printed: 11/12/26 1:25:57 PM 4 UV Retention Time 4 Volts Volts Minutes UV Results Retention Time Area Area % Height Height % Totals

53 Area % Report Page 1 of 1 Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK46-126rohkochSulfonatII.met PM.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 3/23/26 1:27:22 PM Printed: 11/12/26 1:29:16 PM 5 UV Retention Time 5 Volts Volts Minutes UV Results Retention Time Area Area % Height Height % Totals

54 Area % Report Page 1 of 1 Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK136-1-F11-21kochCl3-MeSulfon.met PM171.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 1/2/26 6:6:56 PM Printed: 11/12/26 1:31:49 PM 3 UV Retention Time Volts 1 1 Volts Minutes UV Results Retention Time Area Area % Height Height % Totals

55 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK59-37rohkochCl3-EtSulfon.met PM Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 1:37:19 PM Printed: 11/12/26 11:3:12 PM mau mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

56 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK59-21rohkochCl3-EtSulfon.met AM192.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 5/9/26 12:45:14 PM Printed: 11/12/26 11:8:2 PM mau 6 6 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

57 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK61-2kochCl3-EtSulfon.met PM194.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 4/27/26 5:49:54 PM Printed: 11/12/26 11:9:8 PM mau mau Minutes 5 UV Results Retention Time Area Area Percent Height Height Percent Totals

58 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK13-2rohkochSulfonatPr.met PM182 Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\CH2Cl_PhSulfonatEt.met Acquired: 5/31/26 9:5:21 AM Printed: 11/13/26 9:34:38 AM mau 6 6 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

59 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK13-3rohkochSulfonatPr.met PM183 Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\CH2Cl_PhSulfonatEt.met Acquired: 5/31/26 9:5:56 AM Printed: 11/13/26 9:35:37 AM mau 3 3 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

60 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK76-1rohkochSulfonatPr.met PM181.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 5/29/26 4:53:41 PM Printed: 11/14/26 6:38:32 PM mau 2 2 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

61 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK116-1rohkochCl3-ClEtSulfon.met PM178.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 1:57:32 PM Printed: 11/12/26 11:1:2 PM mau 3 3 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals Ph S H Cl 14d

62 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK116-2rohkochCl3-ClEtSulfon.met PM179.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 11:11:31 PM Printed: 11/12/26 11:11:37 PM mau 3 3 mau Minutes UV Results Retention Time Ph S Area Area Percent Height Height Percent Totals H Cl 14d

63 Area % Report Page 1 of 1 Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK113-2-F6-9kochCl3-ClEtSulfon.met AM171.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 1/4/26 11:38:38 AM Printed: 11/12/26 11:12:28 PM UV Retention Time 1 1 Volts 5 5 Volts Minutes UV Results Retention Time Area Area % Height Height % Totals Ph S H Cl 14d

64 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK12-1rohkochSulton_Bn.met PM173.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 11:18:43 PM Printed: 11/12/26 11:19:15 PM mau mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

65 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK12-2rohkochSulton_Bn.met PM174.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 11:2:37 PM Printed: 11/12/26 11:2:5 PM mau 6 6 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

66 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK99-1rohkochSulton_Bn.met PM172.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 11:16:37 PM Printed: 11/12/26 11:17:2 PM mau 3 3 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

67 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK16-1rohwirklichkochSulton_Me PhEt_Ethanol.met PM173.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 11/12/26 11:23:5 PM Printed: 11/12/26 11:23:28 PM mau mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals

68 Area % Report Data File: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Data\FK16-2rohkochSulton_MePhEt_Et hanol.met PM171.dat Method: C:\EZChrom Elite\Enterprise\Projects\SulfonatII\Method\Cl3-BnSulfon.met Acquired: 6/16/26 3:4:59 PM Printed: 11/12/26 11:24:51 PM mau 2 2 mau Minutes UV Results Retention Time Area Area Percent Height Height Percent Totals